My proposal will attempt to discover the synaptic and cellular changes occurring in the olfactory bulb (OB) that underlie olfactory learning. Norepinephrine (NE), a catecholamine neuromodulator, has been shown to be essential for many forms of olfactory learning in behavioral studies. A recent publication from our lab (Gire and Schoppa, 2008) found that acute exposure to NE facilitates long-term enhancement of synchronized oscillations at the y frequency (30-70Hz), with an effect that lasted up to 60 minutes. The increased synchrony may be involved in olfactory learning since it could increase the importance of specific odor signals sent to downstream cortical centers. There have also been several studies looking at acute, short-term effects of NE on the OB, including a study by Jahr and Nicoll (1982) which found that NE disinhibits mitral cells in the turtle OB at dendrodendritic synapses between mitral cells and GABAergic granule cells. The main goal of my proposal, comprising Aims 1 and 2, is to determine if disinhibition of mitral cells of the type previously seen leads to long-term enhancement of y oscillations. This is a plausible mechanism since acute disinhibition of mitral cells would increase their excitability, which in turn could trigger a rise in intracellular calcium. Increased intracellular calcium is a key component in many forms of long-term synaptic modifications leading to learning. A secondary goal, covered by Aim 3, will be to determine what specific synapse undergoes long-term synaptic modifications. Experiments will be done using whole-cell patch-clamp and local field potential (LFP) recordings from rat OB slices. Elucidating this mechanism will not only explain olfactory learning, but may also reveal how other sensory organs acquire knowledge. While the knowledge acquired through these studies unveils the mechanisms underlying olfactory learning, understanding these inner workings of the brain is essential for treating olfactory dysfunction. Olfactory dysfunction can be an initial sign of serious illnesses, including Parkinson's disease and diabetes, and often greatly reduces enjoyment in life (ref?). This proposal will help the National Institute on Deafness and Other Communications Disorders fulfill their mission to support sensory research.